Evaluation of Empiric Voriconazole Dosing and Therapeutic Drug Monitoring in Hospitalized Pediatric Patients.

SUMMARY: Invasive fungal infections are a significant cause of morbidity and mortality in children with immunodeficiencies. Current dosing recommendations for voriconazole often result in subtherapeutic exposure in pediatric patients. In this single-center retrospective study, we reviewed hospitalized pediatric patients receiving voriconazole with at least one inpatient serum trough concentration measured. Patient characteristics and voriconazole dosing courses with associated trough concentrations were summarized for all patients as well as grouped by age (0 to 1 y, 2 to 11 y, and 12 to 18 y). Of 106 included patients, the median age was 9 years (range, 29 d to 18 y). Five hundred ninety courses of voriconazole were administered with 365 associated troughs. Most troughs were subtherapeutic (49%) and 30% of patients never attained a therapeutic trough. The median oral daily dose associated with a therapeutic trough was higher in younger age groups: 21.6 mg/kg 0 to 1 year, 17.9 mg/kg 2 to 11, and 9.5 mg/kg 12 to 18 years (P<0.001). Patients younger than 2 years had the largest proportion of subtherapeutic troughs and variability in dosing. Attainment of therapeutic voriconazole concentrations was challenging across all pediatric age groups. Higher starting doses for patients younger than 2 years are likely needed.

Letermovir for Cytomegalovirus prophylaxis in pediatric hematopoietic stem cell transplantation.

BACKGROUND: Letermovir (LTV), an antiviral with exclusive activity against Cytomegalovirus (CMV), is approved for prophylaxis of CMV infection and disease in adult hematopoietic cell transplant (HCT) patients. The use of LTV in the pediatric HCT population is off-label, and has limited literature to support its use. PROCEDURE: This was a single-center, retrospective, matched (1:1 LTV:non-LTV) cohort study of allogeneic HCT recipients transplanted at Children's Hospital Colorado from 2015 to 2022. The primary endpoint was clinically significant CMV DNAemia (defined as a CMV viral load >1000 copies/mL or any CMV DNAemia leading to preemptive treatment) through 6 months post transplant. Secondary outcomes included time to clinically significant CMV DNAemia, drug adverse effects, and dose adjustments of concomitant cyclosporine and voriconazole (known drug interactions). RESULTS: We compared 41 patients who received LTV prophylaxis to 41 patients who received no CMV prophylaxis. There was less clinically significant CMV DNAemia through D+180 in the LTV group (9.8% vs. 17.0%, p = .33). Overall, LTV was well tolerated, and 87.8% of patients experienced no adverse effects related to the drug. There was no observed pattern in LTV effect on cyclosporine serum concentrations, but LTV was associated with decreased voriconazole trough levels. CONCLUSIONS: In this retrospective study, the use of LTV prophylaxis in pediatric stem cell patients was associated with reduced clinically significant CMV DNAemia through D+180.

Risk Factors for Venous Thromboembolic Events in Children With Acute Musculoskeletal Infections.

BACKGROUND AND OBJECTIVES: Venous thromboembolic events (VTE) complicate acute hematogenous musculoskeletal infections (MSKIs) among hospitalized children. However, there is limited guidance for which specific MSKI patients are at the greatest VTE risk. This study aimed to identify VTE risk factors for children hospitalized with MSKIs. METHODS: A retrospective chart review was performed of children hospitalized with MSKIs at a single quaternary care pediatric hospital during a 9-year period. Patients with chronic MSKIs, non-hematogenous infections, or significant contributing comorbidities were excluded. Demographic and clinical characteristics were compared between patients with and without VTE using forward stepwise conditional multivariable logistic regression to identify VTE risk factors. RESULTS: Among 335 included patients, 7 (2.1%) developed a VTE. There was no difference in age, sex, or obesity rates for those with or without VTE. Patients with methicillin-resistant Staphylococcus aureus (MRSA) infections and/or critical illness were more likely to develop a VTE with summative adjusted odds ratios of 31.7 and 26.4, respectively. In addition, patients with VTEs had longer hospitalizations (median 4.7 vs. 12.8 d, P <0.001), longer courses of intravenous antimicrobials (median 3.7 vs. 13.5 d, P =0.001), and longer time to fever resolution (median 25.7 vs. 162 h, P =0.004). CONCLUSIONS: VTE prevalence among children with acute MSKIs is low. MRSA infection and critical illness significantly increase the risk for VTE development in these patients. Future prospective studies are needed to determine if VTEs in high-risk MSKI patients can be prevented.

Management of an Immunocompromised Pediatric Patient With Multiple Hospitalizations for Symptomatic COVID-19.

Relapse of infection due to SARS-CoV-2 has been rarely described and there is little guidance regarding the management of such cases in immunocompromised hosts. We present a case of an adolescent female with B-cell acute lymphoblastic leukemia hospitalized multiple times for symptomatic SARS-CoV-2 infection who was safely treated with 2 courses of remdesivir (RDV) and has had no additional readmissions to date. Though additional studies are needed to confirm the safety and efficacy of an additional course of RDV in the setting of relapsed or prolonged severe COVID-19, our observations suggest that a second course of RDV may be considered.

Characteristics of Children With Culture Negative Acute Hematogenous Musculoskeletal Infections.

BACKGROUND: Identifying the causative pathogen for acute hematogenous musculoskeletal infections (MSKIs) allows for directed antimicrobial therapy and diagnostic confidence. However, 20% to 50% of children with acute MSKIs remain culture negative. The objective of this study was to compare characteristics of culture negative MSKI patients to those where a pathogen is identified. METHODS: Electronic medical records of children admitted between July 2014 to September 2018 to a single quaternary care pediatric hospital with acute MSKIs were retrospectively reviewed. Clinical and demographic characteristics were compared between culture positive and culture negative MSKIs. RESULTS: A total of 170 patients were included of whom 43 (25%) were culture negative. All culture negative patients had at least 1 culture type obtained, and the majority (84%) had both blood and source cultures performed. When compared with patients with a causative pathogen identified, culture negative patients were younger (2.3 vs. 9.8 y), smaller (13.5 vs. 31.6 kg), less likely to be febrile on arrival (56% vs. 77%), less likely to have an abscess on imaging (23% vs. 48%), and were more likely to have uncomplicated septic arthritis (35% vs. 8%). No critically ill patient was culture negative. Seven culture negative patients had additional Kingella kingae testing performed, none of which were positive. CONCLUSIONS: Despite targeted and standardized efforts to identify causative bacteria, 25% of children with acute MSKIs never have a pathogen identified. Culture negative patients are younger, less febrile, are less likely to have an abscess, and more likely to have isolated septic arthritis. LEVEL OF EVIDENCE: This is a retrospective cohort study interested in identifying patient characteristics that predict rate of culture positivity for acute MSKIs. This study meets criteria for Level II evidence.

Sustainability of Handshake Stewardship: Extending a Hand Is Effective Years Later.

BACKGROUND: Children's Hospital Colorado created a unique method of antimicrobial stewardship, called handshake stewardship, that effectively decreased hospital anti-infective use and costs in its pilot year (2013). Handshake stewardship is distinguished by: (1) the lack of prior authorization; (2) a review of all prescribed anti-infectives; (3) a shared review by the physician and the pharmacist; and (4) a daily, rounding-based, in-person approach to supporting providers. We sought to reevaluate the outcomes of the program after 5 years of experience, totaling 8 years of data. METHODS: We retrospectively measured anti-infective (antibiotic, antiviral, antifungal) use hospital-wide by unit and by drug for an 8-year period spanning October 2010 to October 2018. Aggregated monthly use was measured in days of therapy per thousand patient days (DOT/1000 PD). The percentage of children admitted ever receiving an anti-infective was also measured, as well as severity-adjusted mortality, readmissions, and lengths of stay. RESULTS: Hospital-wide mean anti-infective use significantly decreased, from 891 (95% confidence interval [CI] 859-923) in the pre-implementation phase to 655 (95% CI 637-694) DOT/1000 PD in post-implementation Year 5; in a segmented regression time series analysis, this was a rate of -2.6 DOT/1000 PD (95% CI -4.8 to -0.4). This is largely attributable to decreased antibacterial use, from 704 (95% CI 686-722) to 544 (95% CI 525 -562) DOT/1000 PD. The percentage of children ever receiving an anti-infective during admission likewise declined, from 65% to 52% (95% CI 49-54). There were no detrimental effects on severity adjusted mortality, readmissions, or lengths of stay. CONCLUSIONS: The handshake method is an effective and sustainable approach to stewardship.

Anti-infective Waste in a Pediatric Institution: Pinpointing Problems in the Process.

Purpose: At Children's Hospital Colorado (CHCO), there are approximately 40 000 inpatient anti-infective orders every year resulting over 100 000 dispenses. Significant quantities of anti-infectives are wasted, incurring roughly $100 000 in waste annually. Identifying areas for improvement will result in cost savings and ameliorate the impact of drug shortages. Summary: This descriptive report discusses the reasons for anti-infective waste at a free-standing, quaternary-care, pediatric hospital. The anti-infectives with the highest cost in waste ($) included meropenem ($38 084), micafungin ($21 690), amphotericin B liposome ($15 913). An internal audit of CHCO anti-infective waste revealed that drugs are wasted for the following reasons: patient discharge, medication order discontinuation or change, and misplaced doses. Conclusion: The CHCO Antimicrobial Stewardship Program and the Pharmacy have proposed 4 process improvement measures that will target anti-infective waste to reduce pharmaceutical waste and hospital costs. These measures may be applicable to other drug classes that likely suffer from a similar proportion of waste.

Increased tenofovir monoester concentrations in patients receiving tenofovir disoproxil fumarate with ledipasvir/sofosbuvir.

BACKGROUND: Intracellular tenofovir diphosphate concentrations are markedly increased in HIV/HCV coinfected individuals receiving tenofovir disoproxil fumarate (TDF) with sofosbuvir-containing treatment. Sofosbuvir may inhibit the hydrolysis of TDF to tenofovir, resulting in increased concentrations of the disoproxil or monoester forms, which may augment cell loading. We sought to quantify tenofovir disoproxil and monoester concentrations in individuals receiving TDF with and without ledipasvir/sofosbuvir. METHODS: HIV/HCV coinfected participants receiving TDF-based therapy were sampled pre-dose and 1 and 4 h post-dose prior to and 4 weeks after initiating ledipasvir/sofosbuvir. Tenofovir disoproxil was not detectable. Tenofovir monoester in plasma and tenofovir diphosphate in PBMC and dried blood spots (DBS) were quantified using LC-MS/MS. Geometric mean ratios (week 4 versus baseline) and 95% CIs were generated for the pharmacokinetic parameters. P values reflect paired t-tests. RESULTS: Ten participants had complete data. At baseline, geometric mean (95% CI) tenofovir monoester plasma concentrations at 1 and 4 h post-dose were 97.4 ng/mL (33.0-287.5) and 0.74 ng/mL (0.27-2.06), respectively. With ledipasvir/sofosbuvir, tenofovir monoester concentrations at 4 h post-dose were 5.02-fold higher (95% CI 1.40-18.05; P = 0.019), but did not significantly differ at 1 h post-dose (1.72-fold higher, 95% CI 0.25-11.78; P = 0.54), possibly due to absorption variability. Tenofovir diphosphate in PBMC and DBS were increased 2.80-fold (95% CI 1.71-4.57; P = 0.001) and 7.31-fold (95% CI 4.47-11.95; P < 0.0001), respectively, after 4 weeks of ledipasvir/sofosbuvir. CONCLUSIONS: Tenofovir monoester concentrations were increased in individuals receiving TDF with ledipasvir/sofosbuvir, consistent with inhibition of TDF hydrolysis. Additional studies are needed to determine the clinical relevance of this interaction.

Small increase in dolutegravir trough, but equivalent total dolutegravir exposure with simeprevir in HIV/HCV seronegative volunteers.

BACKGROUND: Dolutegravir, an HIV integrase strand-transfer inhibitor, and simeprevir, an HCV NS3/4A PI, have the potential to interact as dolutegravir is a P-glycoprotein, uridine glucuronosyl transferase 1A1 and cytochrome P4503A substrate and simeprevir has been shown to mildly inhibit these. OBJECTIVES: To compare dolutegravir and simeprevir pharmacokinetics (PK) when given separately versus in combination. METHODS: Healthy volunteers received: (i) 150 mg of simeprevir once daily for 7 days; (ii) 50 mg of dolutegravir once daily for 7 days; and (iii) 150 mg of simeprevir once daily plus 50 mg of dolutegravir once daily for 7 days, with randomization to treatment sequence. Twenty-four hour intensive PK sampling was performed on day 7 of each sequence following observed dosing and a standardized meal. PK parameters were determined using non-compartmental methods and compared using paired t-tests. Bioequivalence for area under the curve (AUCtau) and maximum concentration (Cmax) were also assessed. NCT02404805. RESULTS: Twenty-four subjects completed all three sequences. Dolutegravir trough was increased 24% (P = 0.0003) with simeprevir. Dolutegravir AUCtau was increased 15% (P = 0.002), but was deemed bioequivalent as the 90% CI for the geometric mean ratio was 107%-123%. Dolutegravir Cmax was bioequivalent. Simeprevir PK was unaffected by dolutegravir. There were no discontinuations due to adverse events and all adverse events were mild to moderate in severity. CONCLUSIONS: Dolutegravir trough was increased slightly with simeprevir, but AUCtau was bioequivalent. Despite the increase in trough, dolutegravir concentrations were well within the range with established safety data. Suggesting that simeprevir and dolutegravir can be safely co-administered.

Effects of sofosbuvir-based hepatitis C treatment on the pharmacokinetics of tenofovir in HIV/HCV-coinfected individuals receiving tenofovir disoproxil fumarate.

Background: The nucleotide analogues tenofovir and sofosbuvir are considered to have low potential for drug interactions. Objectives: To determine the effect of sofosbuvir-based HCV treatment on plasma concentrations of tenofovir and cellular concentrations of tenofovir diphosphate. Methods: HIV-infected participants with acute HCV were treated for 12 weeks with sofosbuvir + ribavirin in Cohort 1 or 8 weeks with ledipasvir/sofosbuvir in Cohort 2 of AIDS Clinical Trials Group study 5327. Only participants taking tenofovir disoproxil fumarate were included in this analysis. Tenofovir in plasma, tenofovir diphosphate in dried blood spots and tenofovir diphosphate in PBMCs were measured pre-HCV therapy and longitudinally during the study using validated LC/MS-MS. Results: Fifteen and 22 men completed Cohorts 1 and 2, respectively. In Cohort 1, tenofovir diphosphate was 4.3-fold higher (95% CI geometric mean ratio 2.46-7.67; P = 0.0001) in dried blood spots and 2.3-fold higher (95% CI 1.09-4.92; P = 0.03) in PBMCs following 12 weeks of sofosbuvir + ribavirin versus study entry. Tenofovir in the plasma was unchanged. In Cohort 2, tenofovir diphosphate was 17.8-fold higher (95% CI 12.77-24.86; P < 0.0001) in dried blood spots after 8 weeks of ledipasvir/sofosbuvir versus study entry. Tenofovir plasma concentrations were 2.1-fold higher (95% CI 1.44-2.91; P = 0.0005). Despite the increase in cellular tenofovir diphosphate concentrations, only a small decline in CLCR (6%-7%) was observed in both cohorts between study entry and end of treatment. Conclusions: These data indicate an unexpected drug interaction with tenofovir disoproxil fumarate and sofosbuvir at the cellular level. Additional studies are needed to determine the mechanism and clinical significance.

Sofosbuvir Plus Ribavirin Without Interferon for Treatment of Acute Hepatitis C Virus Infection in HIV-1-Infected Individuals: SWIFT-C.

Background: Historically, acute hepatitis C virus (HCV) infection was treated with shorter durations of interferon-containing therapies. In the era of direct-acting antivirals (DAAs), it is unclear whether the efficacy of treatment achieved in chronic infection can be maintained with abbreviated courses of therapy during the acute phase. Methods: The sofosbuvir-containing regimens without interferon for treatment of acute HCV in HIV-1 infected individuals (SWIFT-C) is an open-label, 2-cohort clinical trial in which the first cohort assessed for the safety and efficacy of 12 weeks of sofosbuvir plus ribavirin for the treatment of acute HCV infection in participants with chronic human immunodeficiency virus type 1 (HIV-1) infection. This is a preplanned analysis of the first cohort, which had a planned accrual of 17 participants. Results: Seventeen men (11 Hispanic, 6 white, median age 45 years) were enrolled. Most (88%) had HCV genotype-1 infection and few (24%) had the favorable IL28B CC genotype. Median baseline HCV RNA was 2 280 000 IU/mL (interquartile range, 272 000-4 230 000). Ten participants (59%) achieved the primary outcome of SVR12 (90% confidence interval, 36%-78%), failing to establish noninferiority. All treatment failures were due to viral relapse (41%). There were no premature treatment discontinuations. The only factor that differed between participants who achieved SVR vs those who relapsed was ribavirin concentration at the end of treatment. Conclusion: Sofosbuvir-ribavirin for 12 weeks for the treatment of acute HCV genotype-1 infection in HIV-1-infected persons results in a high relapse rate. Preliminary studies of DAA combination therapies suggest improved response rates, although the adequate duration of therapy remains unclear. Clinical Trials Registration: NCT02128217.

Pharmacologic Considerations in the Treatment of Hepatitis C Virus in Persons With HIV.

Roughly one-third of individuals living with the human immunodeficiency virus (HIV) are coinfected with the hepatitis C virus (HCV) due to shared routes of transmission. HIV accelerates the progression of HCV disease; thus, coinfected individuals are at high priority for HCV treatment. Several new HCV therapies, called direct-acting antiviral agents (DAAs), are available that achieve cure rates of >90% in many patient populations including individuals with HIV. The primary consideration in treating HCV in HIV-infected persons is the potential for drug interactions. We describe the clinical pharmacology and drug interaction potential of the DAAs, review the interaction data with DAAs and antiretroviral agents, and identify the knowledge gaps in the pharmacologic aspects of treating HCV in individuals with HIV coinfection. This review will focus on DAAs that have received regulatory approval in the United States and Europe and agents in late stages of clinical development.

Tenofovir, emtricitabine, and darunavir/ritonavir pharmacokinetics in an HIV-infected patient after Roux-en-Y gastric bypass surgery.

OBJECTIVE: To determine antiretroviral (ARV) pharmacokinetics in a patient who previously underwent Roux-en-Y gastric bypass (RYGB) surgery. CASE SUMMARY: We describe a 38-year-old Hispanic man who tested positive for human immunodeficiency virus (HIV) 11 months following RYGB surgery. When the patient presented for care of his HIV, his HIV-1 RNA was 146 138 copies/mL (5.20 log) and his CD4 T cell count was 320 cells/mm(3) (25%). He was initiated on tenofovir disoproxil fumarate (TDF) 300 mg once daily, emtricitabine (FTC) 200 mg once daily, and darunavir/ritonavir (DRV/r) 600/100 mg twice daily. ARV concentrations were similar to historical data. Six months following ARV initiation, HIV-1 RNA was <48 copies/mL and CD4 count had increased to 562 cells/mm(3) (39%). DISCUSSION: Bariatric surgery has been successfully performed in obese persons infected with the HIV, but data are limited on ARV drug selection and pharmacokinetics in this group. Optimal suppression of HIV replication requires appropriate concentrations of ARV drugs, and in a patient who has undergone RYGB, this can be challenging not only because of a decreased absorptive surface area but also because of an increased intragastric pH. CONCLUSION: We found that once daily TDF/FTC and twice daily DRV/r produced trough concentrations similar to historic data in a patient who previously underwent RYGB with virologic suppression and immunologic recovery.

At the break point: What needs to change for antimicrobial stewardship program pharmacists?

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

Time to positivity of blood cultures in a level IV NICU varies based on organism category and population subgroups: is a 36-hour rule out safe?

BACKGROUND: Time to positivity (TTP) of blood cultures and organism characteristics may be different in a Level IV NICU population. METHODS: Retrospective study of 309 Level IV NICU positive blood cultures between January 2012 to December 2018 describing TTP and organism characteristics. RESULTS: Median TTP [IQR] was 21.1 [14.3, 25.2] hours, with 91.2% positive at 36 h, and 96.1% positive at 48 h. Gram negative definite pathogens had the shortest TTP (13.0 [11.4, 15.4] hours) compared to gram positive definite pathogens (16.3 [13.0, 22.4] hours). TTP for treated gram positive commensal organisms (22.3 [20.1, 30.4] hours) and those considered contaminants (23.6 [21.4, 26.0] hours), was significantly longer than both gram positive and negative definite pathogens. CONCLUSION: When antimicrobials are initiated due to concern for bacteremia and blood cultures have not identified a causative pathogen at 36 h, antimicrobials may be safely discontinued in the majority of Level IV NICU patients.

Guidance for prevention and management of COVID-19 in children and adolescents: A consensus statement from the Pediatric Infectious Diseases Society Pediatric COVID-19 Therapies Taskforce.

BACKGROUND: Since November 2019, the SARS-CoV-2 pandemic has created challenges for preventing and managing COVID-19 in children and adolescents. Most research to develop new therapeutic interventions or to repurpose existing ones has been undertaken in adults, and although most cases of infection in pediatric populations are mild, there have been many cases of critical and fatal infection. Understanding the risk factors for severe illness and the evidence for safety, efficacy, and effectiveness of therapies for COVID-19 in children is necessary to optimize therapy. METHODS: A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacology, and pediatric intensive care medicine from 21 geographically diverse North American institutions was re-convened. Through a series of teleconferences and web-based surveys and a systematic review with meta-analysis of data for risk factors, a guidance statement comprising a series of recommendations for risk stratification, treatment, and prevention of COVID-19 was developed and refined based on expert consensus. RESULTS: There are identifiable clinical characteristics that enable risk stratification for patients at risk for severe COVID-19. These risk factors can be used to guide the treatment of hospitalized and non-hospitalized children and adolescents with COVID-19 and to guide preventative therapy where options remain available.

Microbiology Culture Results and Antibiotic Prescribing in Pediatric Patients With Lymphadenitis.

BACKGROUND: Bacterial lymphadenitis is a common reason for antibiotic treatment and hospitalization in children. The literature available addressing the bacterial etiology of lymphadenitis recommends the use of narrow-spectrum agents to cover common pathogens. We suspect that patients at our institution receive unnecessarily broad-spectrum antimicrobial agents. The primary objective of this study was to characterize the microbiology and antibiotic use in lymphadenitis patients. METHODS: Retrospective review of children admitted over a 10-year period with an International Classification of Diseases Ninth or Tenth Edition code for lymphadenitis. Patients were included if they were <18 years old, admitted to the inpatient ward, and had intraoperative lymph node cultures collected. RESULTS: A total of 131 patients admitted with lymphadenitis had lymph node cultures collected and were included. Seventy-two (72/131; 55%) patients had positive lymph node culture results with pathogenic bacteria. The predominant pathogens were Staphylococcus aureus (56/72; 77.8%) and Streptococcus pyogenes (10/72; 13.9%). The most common inpatient empirical regimen was ampicillin-sulbactam. Of the 72 patients with typical pathogens identified, 80.6% were sensitive to a first-generation cephalosporin, whereas 86.1% were sensitive to a ß-lactam/ß-lactamase inhibitor. CONCLUSION: Patients presenting to our institution with acute bacterial lymphadenitis were predominantly found to have methicillin-susceptible S. aureus lymphadenitis that could be empirically treated with cefazolin. At our institution, there is little advantage to the most commonly used broad-spectrum agent, ampicillin-sulbactam.

Pharmacological Management of Pediatric Clostridioides difficile Infection: Clarifying the Controversies.

Clostridioides difficile infection (CDI) is a major public health concern for pediatric and adult patients. The management of pediatric CDI poses a challenge to healthcare providers due to lack of strong randomized controlled trials to guide pharmacological management. Additionally, recent updates to CDI guidelines recommend oral vancomycin over metronidazole for the management of CDI in adults, leaving questions regarding how to best manage pediatric patients. This continuing education pharmacotherapy review describes available evidence for the safety and efficacy of medications used in the treatment and management of pediatric CDI and aims to clarify discrepancies between pediatric and adult recommendations.

Identifying predictors for source culture positivity in children with acute musculoskeletal infections.

OBJECTIVES: Identifying the causative bacterial pathogen for children with acute hematogenous musculoskeletal infections (MSKIs) allows for improved care. The purpose of our study was to determine if clinical markers could predict which patients will have a causative pathogen found on source culture alone, thus being highest yield to undergo operative diagnostic procedures. METHODS: A single-center, retrospective cohort study was performed. Medical records for patients between 6 months and 18 years of age admitted between July 2014 and September 2018 with a discharge diagnosis of acute osteomyelitis, septic arthritis, or pyomyositis were reviewed. Patients were stratified based on results of blood and source cultures. Predictors of interest were screened on a univariable basis with significant predictors retained in a multivariate analysis. RESULTS: There were 170 patients included. No predictors were significantly associated with increased odds of having a causative pathogen found on source culture alone. Degree of C-reactive protein elevation and history of fever were associated with decreased odds of being source culture positive, OR (95% CI); 0.92 (0.87, 0.98) and 0.39 (0.19, 0.81), respectively. CONCLUSIONS: Predictive modeling failed to identify children with MSKIs whose causative pathogen was found by source culture alone. It is difficult to predict which MSKI patients will be highest yield for operative diagnostic procedures.

Prolonged Perioperative Antibiotics: A Hidden Problem.

OBJECTIVES: National guidelines generally recommend 24 hours or less of surgical antibiotic prophylaxis. In a freestanding, regional children's hospital, we evaluated the duration of antibiotic surgical prophylaxis to identify targets for standardization of practice. METHODS: All procedures performed in 2017 were extracted from our local data warehouse; those involving an incision were considered a surgical procedure and correlated to antibiotic data. Antibiotic courses were reviewed if administered for >24 hours, or if the duration or indication for prophylaxis was uncertain. Total duration of prophylaxis (including discharge prescriptions) was calculated in hours for all procedures and categorized by department and by the quantity of prophylaxis received: none, single dose, multiple doses within 24 hours, and >24 hours. Percentage of procedures and total days of potential excess were calculated. RESULTS: A total of 15 651 procedures were included; 5009 met criteria for chart review, and after further exclusions, 12 895 procedures were included in the analysis. In total, 55% of all 12 895 procedures received prophylaxis. A single dose was given in 30%. Over 24 hours was administered in 11%, and 14% received multiple doses <24 hours (both potential excess). Results were evaluated by surgical subspecialty and procedure type. There were 5733 cumulative days of surgical prophylaxis administered after 24 hours (potential excess). CONCLUSION: In 2017, up to 25% of procedures received potentially unnecessary perioperative prophylaxis, indicating that national guidance specific to pediatrics would have high impact on antibiotic overuse in the pediatric surgical population.